ArticleMolecular and cellular biology2010
Nuclear alpha NAC influences bone matrix mineralization and osteoblast maturation in vivo.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- The biological function of integrin-linked kinase on bone formation.Bone reports · 2025Review
- Study of Podoplanin-Deficient Mouse Bone with Mechanical Stress.Dentistry journal · 2025Article
- The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA.Nucleic acids research · 2022Article
- NACA and LRP6 Are Part of a Common Genetic Pathway Necessary for Full Anabolic Response to Intermittent PTH.International journal of molecular sciences · 2022Article
- Protein phosphatase 1 regulatory subunit 18 suppresses the transcriptional activity of NFATc1 via regulation of c-fos.Bone reports · 2021Article
- The association between vitamin K and medial tibial-femoral knee osteoarthritis progression: Data from the osteoarthritis initiative.Osteoarthritis and cartilage open · 2021Article
- Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment.Scientific reports · 2021Article
- Ciliopathic micrognathia is caused by aberrant skeletal differentiation and remodeling.Development (Cambridge, England) · 2021Article
- Dephosphorylation of the transcriptional cofactor NACA by the PP1A phosphatase enhances cJUN transcriptional activity and osteoblast differentiation.The Journal of biological chemistry · 2019Article
- Loss ofAmerican journal of physiology. Endocrinology and metabolism · 2019Article
- Expression and Dynamics of Podoplanin in Cultured Osteoblasts with Mechanostress and Mineralization Stimulus.Acta histochemica et cytochemica · 2018Article
- αNAC inhibition of the FADD-JNK axis plays anti-apoptotic role in multiple cancer cells.Cell death & disease · 2014Article
- The PTH-Gαs-protein kinase A cascade controls αNAC localization to regulate bone mass.Molecular and cellular biology · 2014Article
- Article
- Comparative in vitro study regarding the biocompatibility of titanium-base composites infiltrated with hydroxyapatite or silicatitanate.Journal of biological engineering · 2014Article
- Unfolding of the C-terminal domain of the J-protein Zuo1 releases autoinhibition and activates Pdr1-dependent transcription.Journal of molecular biology · 2013Article
- Extracellular matrix mineralization promotes E11/gp38 glycoprotein expression and drives osteocytic differentiation.PloS one · 2012Article
- Combinatorial control of ATF4-dependent gene transcription in osteoblasts.Annals of the New York Academy of Sciences · 2011Review
- Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption.Journal of cellular biochemistry · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nascent-polypeptide-associated complex and coactivator alpha (alpha NAC) is a protein shuttling between the nucleus and the cytoplasm. Upon phosphorylation at residue serine 43 by integrin-linked kinase, alpha NAC is translocated to the nuclei of osteoblasts, where it acts as an AP-1 coactivator to increase osteocalcin gene transcription. To determine the physiological role of nuclear alpha NAC, we engineered a knock-in mouse model with a serine-to-alanine mutation at position 43 (S43A). The S43A mutation resulted in a decrease in the amount of nuclear alpha NAC with reduced osteocalcin gene promoter occupancy, leading to a significant decrease in osteocalcin gene transcription. The S43A mutant bones also expressed decreased levels of alpha(1)(I) collagen mRNA and as a consequence had significantly less osteoid tissue. Transient transfection assays and chromatin immunoprecipitation confirmed the alpha(1)(I) collagen gene as a novel alpha NAC target. The reduced quantity of bone matrix in S43A mutant bones was mineralized faster, as demonstrated by the significantly reduced mineralization lag time, producing a lower volume of immature, woven-type bone characterized by poor lamellation and an increase in the number of osteocytes. Accordingly, the expression of the osteocyte differentiation marker genes DMP-1 (dentin matrix protein 1), E11, and SOST (sclerostin) was increased. The accelerated mineralization phenotype was cell autonomous, as osteoblasts isolated from the calvaria of S43A mutant mice mineralized their matrix faster than did wild-type cells. Thus, inhibition of alpha NAC nuclear translocation results in an osteopenic phenotype caused by reduced expression of osteocalcin and type I collagen, accelerated mineralization, and immature woven-bone formation.
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